Background
We have previously shown that
angiopoietin-like 4 (
angptl4) mRNA, a hypoxia-inducible gene, is highly expressed in clear cell renal-cell carcinoma (ccRCC), the most common subtype of RCC for which no specific marker is available. We here investigated whether
angptl4 mRNA 1) could be a useful diagnostic and/or prognostic marker of ccRCC in a large and comprehensive retrospective series, 2) induction is dependent on the
VHL status of tumors.
Methodology/Principal Findings
Using
in situ hybridization, we report that
angptl4 mRNA is expressed in 100% of both sporadic (n = 102) and inherited (n = 6) primary ccRCCs, without any statistical association with nuclear grade (
p = 0.39), tumor size (
p = 0.09), stage grouping (
p = 0.17), progression-free survival (
p = 0.94), and overall survival (
p = 0.80).
Angptl4 mRNA was also expressed in 26 (87%) of 30 secondary ccRCCs but neither in any other secondary RCCs (n = 7). In contrast,
angptl4 mRNA was neither expressed in 94% non-ccRCC renal tumors (papillary RCCs (n = 46), chromophobe RCCs (n = 28), and oncocytomas (n = 9)), nor in non-renal clear cell carcinomas (n = 39).
Angptl4 expression was also examined in tumors associated (n = 23) or not associated (n = 66) with VHL disease. 40 (98%) hemangioblastomas expressed
angptl4 whereas all pheochromocytomas (n = 23) and pancreatic tumors (n = 25) were
angptl4-negative, whatever their
VHL status.
Conclusions/Significance
A
ngptl4 mRNA expression was highly associated with ccRCC (
p = 1.5 10
−49, Chi square test) allowing to define its expression as a diagnosis marker for primary ccRCC. Moreover,
angptl4 mRNA allows to discriminate the renal origin of metastases of clear-cell carcinomas arising from various organs. Finally, inactivation of
VHL gene is neither necessary nor sufficient for
angptl4 mRNA induction.
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